The ultimate goal of our project is to develop novel therapeutics effective in chronic kidney diseases that normally develop fibrosis, lead to end stage renal disease and require renal replacement therapy. This will be achieved by identifying novel selective functional antagonists for the lysophosphatidic acid (LPA) type 1 receptor. Our drug discovery approach will synthesize novel compounds free of drug-drug interaction risks that demonstrate selective, functional antagonism of the LPA-1 receptor. Their effectiveness will be confirmed using a series of high throughput cell-based assays. Candidate molecules will then be evaluated for their ability to prevent the progression of renal fibrosis in a unilateral ureteral obstruction (UUO) animal model. The intent of this Phase 1 study is to identify at least one novel series of molecules for lead optimization in a Phase 2 program. PUBLIC HEALTH RELEVANCE: The objective is to discover and develop new drugs for treating chronic kidney diseases that involve renal fibrosis, a significant cause of mortality.